riboflavin-5′-phosphate

I previously published “Homocysteine Genetics – Coenzyme B Vitamins” in which I considered in-depth how homocysteine (an intermediate chemical in the Methylation Cycle) is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways. I also wrote “Folate Ingredients – Folinic Acid & 5-MTHF” which discussed how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today’s article, I take a broader view of the topic that encompasses the Methylation Cycle, genetics, and B vitamins.

THE METHYLATION CYCLE

The Methylation Cycle is considered to be one of the most important metabolic pathways in the human body. Its most important function is to provide methyl groups via SAM (S-adenosyl methionine) to hundreds of different body substrates. Methylation is continually occurring in the body, transforming many millions of molecules throughout the body every second. Molecules receive methyl groups, then separate and recombine continuously, transforming and reforming constantly in the ongoing process of life!

As a reminder of the pathways involved in the Methylation Cycle, the following figure provides a flow chart showing the details.

Figure 1. Metabolic Pathways in Methylation Cycle

A key purpose of this cycle is to provide methyl groups (CH3) needed by a broad range of of body functions (over 200 different functions). Examples include:

Influences the genetic expression that parents give their children and helps guide the development of the embryo.

Is needed by the nervous system to produce neurotransmitters and maintain the nerves.

Mobilizes fats and cholesterol so they do not accumulate where they are harmful, such as the arteries and liver.

Helps repair damaged proteins in the cells so they can function properly.

Protects the DNA in the genome (genetic code) to reduce the chances of mutation.

Creates antioxidants used in the antioxidant defense system.

DESCRIPTION OF PATHWAYS WITHIN THE METHYLATION CYCLE

The overall flow of the Methylation Cycle begins with dietary methionine (an essential amino acid) which combines with ATP (adenosine triphosphate – body energy) to form SAM (S-adenosyl methionine) – the common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. When SAM transfers a methyl group to a body chemical the residue from this reaction leads to the production of homocysteine.

Homocysteine can be converted in the transsulfuration pathway that requires coenzyme vitamin B6 to produce cysteine, glutathione, taurine, and sulfates. These sulfur containing substances provide important antioxidant protection and detoxification functions in the body.

Homocysteine can be converted back to methionine through the betaine (trimethyl glycine) pathway which requires zinc and magnesium. This pathway also requires dietary betaine or choline which the body can convert into betaine.

Also, homocysteine can be converted back to methionine via the remethylation pathway which requires 5-MTHF, coenzyme vitamin B2 and methylcobalamin (B12).

GENETICS

It is important to understand that each of the pathways described above are able to be executed only in the presence of enzymes (shown in blue boxes in the diagram) created by specific genes in your genetic code. For example, Betaine-Homocysteine S-Methyltransferase (BHMT) is the enzyme required in the betaine pathway, Cystathione Beta Synthase (CBS) is the enzyme required in the transsulfuration pathway, and Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase (MS) are enzymes required in the remethylation pathway.

Assuming that you have perfect genetics (no mutations, SNPs, free radical damage, insertions/deletions, etc.), the proper functioning of these pathways are still subjected to the fact that the required vitamins and minerals (vitamin B6, vitamin B2, Folate, vitamin B12, zinc, magnesium, and betaine) need to be provided by your diet or from supplements for the body to function correctly.

In addition, exposure to high levels of toxins from your environment and high levels of stress require that the nutritional needs will be even higher for the pathways to work properly. For example, exposure to high levels of toxins requires that the transsulfuration pathway be more active possibly reducing the amount of available methionine to support necessary methyl transfer reactions.

For these reasons alone the consensus of knowledgeable practitioners is that you should be eating an organic whole foods diet, taking appropriate nutritional supplements, avoiding and eliminating toxins from food, water, and air (living in a clean environment), and avoiding an unduly stressful life. All of these actions fall into the category of Epigenetics which you generally have control over!! Doing these things alone could significantly balance the functioning of your Methylation Cycle and improve your health.

Unfortunately, few people have perfect genetics which often causes the various pathways in the Methylation Cycle to become imbalanced and unable to correct the dysregulation imposed upon the body. For example, the enzyme MTHFR can have heterozygous (single chromosome) genetic variations in up to 50% of certain populations and homozygous genetic variations (both chromosomes) in 10% or more of certain populations.

Some disorders that researchers have associated with MTHFR genetic variations include:

Alzheimer’s disease

Asthma

Atherosclerosis

Autism

Bipolar disorder

Bladder issues

Blood clots

Breast problems

Chemical sensitivity

Chronic fatigue syndrome

Down syndrome

Epilepsy

Fibromyalgia

Gastric problems

Glaucoma

Heart murmurs

High blood pressure

Irritable bowel syndrome

Leukemia

Male infertility

Methotrexate toxicity

Migraines with aura

Multiple sclerosis

Myocardial infarction

Nitrous oxide toxicity

Parkinson’s disease

Pulmonary embolisms

Schizophrenia

Stroke

Thyroid issues

Unexplained neurologic disease

Vascular dementia

This extensive list is highly significant and tells us that it is very important to have genetic testing done for the genes/enzymes in the Methylation Cycle pathway. I prefer the BodySync genetic test which evaluates the key Methylation Cycle genes plus many other important genes in a single test.

B VITAMINS AND MINERALS

We are strong believers that everyone should start their nutritional program by eating a balanced, organic, whole foods diet. We have been doing this ourselves for the past 30 years. Unfortunately, only a small percentage of people follow this advice and in most cases this leads to poor nutritional status that does not adequately support the body’s needs. This is especially true with respect to obtaining the nutrients needed to support the Methylation Cycle.

Nine of our family members and associates have taken the BodySync genetic test which evaluates the condition of 45 different enzymes including CBS, MTHFR (2 variations), MTR (related to B12 and 5-MTHF as they relate to methionine synthase – MS), and MTRR (related to maintaining B12 levels needed by the MTR enzyme). In every case the results showed at least 2 and up to 4 enzymes had genetic variations. These results indicate that the nutritional requirements for folate as 5-MTHF, vitamin B12 as methylcobalamin, vitamin B6, vitamin B2, magnesium and zinc will likely be significantly greater than normal.

Given the above information, it seems essential for good health to take nutritional supplements that provide the important nutrients. Below I will discuss various formulas that I have developed and refined over many years that are useful especially for the Methylation Cycle.

MULTIVITAMINS

When looking at the total needs the body has for nutrients that the body does not produce, including fat soluble vitamins (A, D (some), E, K1 and K2), vitamin C, B vitamins (B1, B2, B3, B5, B6, folate, B12, biotin, choline, and inositol), minerals (Ca, Mg, Zn, Se, Cu, Mn, Cr, Mo, K, boron, and vanadium), and betaine it only seems wise to include as a top priority a Multivitamin that includes all of these in what I term therapeutic amounts (carefully selected after evaluating thousands of research studies carried out over many years.)

In this context, it is important to recognize that every enzymatic reaction in the body requires mineral cofactors in order to carry out its function. A good multivitamin provides many of these required minerals.

Additionally, the multivitamin should contain ingredient forms that research has confirmed to be the most absorbable and usable by the body. These include coenzyme B vitamins, Krebs cycle (citrate, alpha-ketoglutarate, succinate, fumarate, & malate) minerals, and amino acid chelates.

In the context of supporting the Methylation Cycle we are looking for specific forms and amounts of B vitamins that can adequately provide the body’s needs. The means that there should be coenzyme folate as 5-MTHF of at least 400 mcg, coenzyme vitamin B-12 as methylcobalamin of at least 200 mcg, Vitamin B6 (including significant amounts of pyridoxal 5′ phosphate) of at least 40 mg, and Vitamin B2 (including significant amounts of riboflavin 5′ phosphate) of at least 25 mg. In addition, magnesium (100 mg) and zinc (at least 20 mg) should be provided.

Please note that the body’s requirements for magnesium is generally accepted by nutritional experts to be higher than 400 mg daily (and as high as 1,000 mg daily). For this reason we generally recommend that a person take supplemental magnesium (such as HPDI’s MYO-MAG) at levels over 400 mg daily.

The two multivitamin formulas Health Products Distributors provides for adults that meet these requirements (and more) are the Hank & Brian’s Mighty Multi-Vite and Multi Two (in both capsule and tablet forms). Click on the bottles below for technical details.

B COMPLEX

In situations where significant genetic variations are present it may be wise to add a B COMPLEX supplement to the MULTIVITAMIN to provide even larger amounts of the needed B vitamins. HPDI provides a B-Complex-50 product that includes significant amounts of coenzyme forms and contains 50 mg of Vitamin B1, 50 mg of Vitamin B2, 100 mg of Vitamin B3, 50 mg of Vitamin B6, 500 mcg of coenzyme folate (both folinic acid and 5-MTHF), 100 mcg of B12 (both methylcobalamin and hydroxocobalmin), 50 mg of Vitamin B5 (pantothenic acid), 500 mg of Biotin, 50 mg of choline, and 50 mg of inositol. Click on the bottle below for technical details.

FOLATE AS 5-MTHF

In situations where an inadequate diet is present and genetic testing indicates an MTHFR variation (especially a homozygous variation) Health Products Distributors provides a 5-MTHF folate supplement that easily absorbs into the body and can be directly used in combination with Vitamin B12 to convert homocysteine to methionine. Click on the bottle below for technical details.

5-MTHF 1 mg in veggie cap

B-12 as METHYLCOBALAMIN

It is often the case for older patients and vegetarians that Vitamin B12 is deficient. In these cases it is wise to supplement with a significant amount of methylcobalamin to ensure that the Methylation Cycle has sufficient to effectively convert homocysteine into methionine. Health Products Distributors Vitamin B12 contains 5 mg of methylcobalamin in sublingual lozenge form that supports excellent absorption even if swallowed and absorbed by diffusion. Click on the bottle below for technical details.

Vitamin B-12 – 5 mg Methylcobalamin sublingual lozenge.

MINERALS

Magnesium and zinc are two important minerals used in the betaine pathway of the Methylation Cycle in which homocysteine is converted back to methionine.

In the body magnesium is involved in more than 400 essential metabolic reactions and is required by the adenosine triphosphate (ATP)-synthesizing protein in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium (MgATP). Therefore, it also is involved in converting methionine to SAM.

Over 300 different enzymes depend on zinc for their ability to catalyze vital chemical reactions. Zinc-dependent enzymes can be found in all known classes of enzymes.

Health Products Distributors provides 100 mg magnesium/vcap in its MYO-MAG supplement which is especially important in increasing ATP in the Krebs Cycle. This product also contains vitamin B1, vitamin B2, and vitamin B6 with substantial amounts of coenzyme forms and manganese. Click on the bottle below for technical details.

MYO-MAG with 100 mg magnesium per serving and key B vitamins.

Health Products Distributors provides 25 mg zinc/serving in its Double Zinc Plussupplement. This formula provides zinc in the picolinate and citrate forms as well as 3 mg of P5P (coenzyme B6). Click on the bottle below for technical details.

Double Zinc Plus supplement with P5P and 25 mg zinc

SUMMARY

The Methylation Cycle is recognized as one of the most important metabolic pathways in the human body. When not properly supported by key B vitamins and minerals, the Methylation Cycle can become severely imbalanced which can lead to a very wide range of poor health conditions. Furthermore, genetic variations in the genes that produce important enzymes allowing the Methylation Cycle to function correctly lead to even further imbalances and greater possibility for conditions of poor health.

In this article, I have provided insight into how the Methylation Cycle works and how it can be significantly supported by lifestyle changes regarding diet and environment (Epigenetics) and by specific B vitamins and mineral supplements that I have developed over many years. In addition, we have shown that knowledge gained from genetic testing can further provide a critical understanding of your specific needs so that your health can be optimized.

Looking for an advanced antioxidant formula? Already using or recommending vitamin C? Curious about cellular Nrf2 activation? Look no further than PRO-C™.

PRO-C™ is among the most effective antioxidant formulas available. It is an HPDI foundational supplement that works most effectively when used with multivitamins, essential fats, and superfoods. However, it is also an excellent standalone formula that can rapidly provide the body with extremely high protection from free radicals.

We ourselves have taken PRO-C daily for many years with excellent results. Our personal experience together with detailed feedback from health professionals and end-users affirms the effectiveness of PRO-C as a super-antioxidant–vitamin C-Nrf2 activator formula.

PRO-C provides 500 mg of buffered vitamin C per capsule (buffered with calcium, magnesium, and zinc) along with grape extract (seed, skin, pulp) and green tea extract (95% polyphenols). In addition, we include a special combination of the “network antioxidants” l-glutathione (reduced), n-acetyl-l-cysteine (NAC), r-lipoic acid, and selenium. Vitamin B2 and Vitamin B6 in coenzyme forms support the enzymatic effectiveness of the “network antioxidants”. The formula works so well because this combination of ingredients leverages the antioxidant power of vitamin C, grape extract, green tea extract, and the other nutrients to act synergistically in order to maximize effectiveness.

FORMULATION HISTORY AND THE SCIENCE BEHIND PRO-C™

What you may not know is the history of the development PRO-C and the scientific knowledge on which Dr. Hank Liers based his formulation of it.

Dr. Hank formulated his first product in 1989. It was a potent antioxidant formula he called PYC-C™ (sounds like “pixie”). PYC-C consisted of a combination of buffered Vitamin C (including magnesium, calcium, and zinc ascorbates) and pycnogenols from pine bark.

By 1997 Dr. Hank had gathered a great deal of new scientific information regarding green tea catechins and the nutrients termed “network antioxidants” by Dr. Lester Packer, director of Packer Lab at University of California, Berkeley. Beyond this information, Dr. Hank studied additional research regarding how various nutrients worked together synergistically. At that point, he was ready to formulate the new, improved PRO-C™ super antioxidant formula.

HPDI launched PRO-C™ in late 1997. It rapidly became one of our best-selling products. Our customers raved about how effective it was for them if they felt like they were “coming down with something” (like a cold, flu, virus, infection, etc.). Greater skin elasticity greatly helped pregnant women avoid stretch marks and episiotomies. Today, we highly recommend its use together with our other Foundational Supplements to ensure optimal health and anti-aging effects.

THE PRO-C™ SUPER ANTIOXIDANT FORMULA

PRO-C™ super antioxidant formula is extremely synergistic, especially in so far as it increases the body’s ability to quench free radicals in its aqueous (i.e., water-based) compartments. Because antioxidants may become free radicals themselves after they have done their job, the body has developed an elaborate system for recovery of oxidized antioxidants.

Dr. Lester Packer was the primary researcher investigating the synergistic character of antioxidants. He made this statement in his interview with Dr. Richard Passwater after publication of Packer’s The Antioxidant Miracle (1999):

” [The major theme of] The Antioxidant Miracle is that antioxidants work in a coordinated manner. They interact with one another, and this interaction, which we like to call the antioxidant network, is very important to the overall antioxidant defense that we possess. The key members of the antioxidant network are vitamin E and vitamin C, but there are other participants in this network. These are thiol antioxidants, antioxidants that contain sulfur groups in the body. Glutathione perhaps is the best known of these, but there are other sulfur-containing antioxidants that also are very important.”

Dr. Packer continues:

“This whole antioxidant network works like an orchestra depending on individuals who have, of course, different complements of antioxidants depending upon their nutritional regimens and the individuality of their own body metabolisms. The idea behind having a network of antioxidants is that if one antioxidant happens to be deficient the others can compensate and still keep the antioxidant defense system strong.”

The following diagram shows some of the relationships in the antioxidant network and how they support each other.

Figure 1 – Dr. Packer’s Antioxidant Network

We see, for example, reduced glutathione (GSH) has the ability to reduce oxidized Vitamin C back to its unoxidized state. Vitamin C reduces oxidized Vitamin E back to its unoxidized state, and both reduces glutathione and spares it for other important functions, including detoxification and immune enhancement.

Many polyphenols (e.g., oligomeric proanthocyanidins (OPCs), anthocyanidins and catechins) found in red grape and green tea extracts spare Vitamin C and glutathione in the body, as well as operate as powerful antioxidants, anti-inflammatories, and connective tissue strengtheners.

R-Lipoic Acid (see abstracts below) operates as an antioxidant both in its oxidized and reduced states, reduces the oxidized forms of both Vitamin E and Vitamin C, and and has been shown to enhance glutathione levels. Because several of these substances are able to protect Vitamin E contained in cell membranes, this combination also has a significant beneficial effect on the fat soluble antioxidant status of the body!

The nutrients in PRO-C have been carefully selected and balanced to provide optimal effects, especially as related to free radical protection, detoxification, immune system enhancement, connective tissue strengthening, and reduction of inflammation. PRO-C therefore provides outstanding nutritional support in a wide variety of conditions of poor health, as well as acts to support and maintain a state of health and well-being.

It the last several years the research results on Nrf2 activators have become well known and products developed that take advantage of these nutrients. For details see our blog article Natural Phytochemical Nrf2 Activators for Chemoprevention. Researchers have been studying specifically how enzyme-activating substances such as OPCs and anthocyans activate a transcription factor known as Nrf2 that causes the body to endogenously produce higher levels of a wide variety of protective enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase.

Although we did not know about Nrf2 activators in 1997 when we formulated PRO-C, we have subsequently learned that four of the ingredients in the formula have powerful Nrf2 activity. These include grape seed extract, green tea extract, NAC, and r-lipoic acid. With this knowledge, we now understand that PRO-C provides both powerful external antioxidants (with extremely high ORAC5.0 values) that support redox cycles within the body, but also provides ingredients that allow the body to endogenously produce powerful protective enzymes for even greater free-radical protection and health.

Below we will discuss each ingredient and show some of the research that confirms its effectiveness.

VITAMIN C

Vitamin C typically is called l-ascorbic acid or ascorbate and is an essential nutrient for humans and other animal species. The term “vitamin C” refers to a number of vitamins that have vitamin C activity in animals, including ascorbic acid and its salts (e.g., magnesium ascorbate, calcium ascorbate, sodium ascorbate, etc.), and some oxidized forms such as dehydroascorbate and semidehydroascorbate.

Vitamin C is known to perform many critical functions within the body involving detoxification, tissue building, immune enhancement, pain control, and controlling or killing pathogenic organisms. It is also known to be helpful for wound and bone healing, healthy skin and eyes, fighting infections, stress control, toxic exposure, and repairing damaged tissue of all types. For much more information on the many benefits of Vitamin C see our blog article Vitamin C – An Amazing Nutrient.

Below are two abstracts that show some of the beneficial effects of Vitamin C when used with other network antioxidants:

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L- cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

Vitamins A, C, and E act as antioxidants and as free radical scavengers in biological systems. Glutathione is involved in several reactions in vitamin metabolism and also plays an important role in cell membrane protection against lipid peroxidation by free radicals. We sought to use these natural defense mechanisms against oxygen free radicals formed during reperfusion of ischemic skin flaps. An acute axial random skin flap model was utilized in the rat. Vitamins or glutathione were administered by oral gastric tube or intravenously in the perioperative period, and survival of the flap was measured at 1 week. Glutathione, beta-carotene, ascorbic acid and alpha-D- tocopherol showed mean flap survival of 84% to 89%, each of which was significantly improved over saline controls (67% p less than .0005). The mechanisms and biochemistry of these vitamins, and their interactions with other vitamins and with glutathione, are discussed, along with clinical implications of free radical scavenging and skin flap survival.

GRAPE EXTRACT

Grape extract (seeds, skin, pulp) contain highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape seed extract are able to strengthen collagen fibers in aging or damaged connective tissue and can act as a preventative against connective tissue degradation.

Some research indicates that anthocyans, which are found in extracts of grape skin and stems (but not in grape seed extract), can reduce oxidized glutathione while at the same time become reduced themselves. In addition, extracts of grape skin and stems (but not those of grape seed extract) contain a material called trans-resveratrol that has been shown to have chemopreventive effects.

1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA- induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.

BACKGROUND: The pharmacological treatment of non-complicated chronic venous insufficiency is a current and well-debated topic. The introduction of new products with action on the venous system, improved knowledge on the physiopathology of venous insufficiency and the possibility provided by new analytical instruments, have given new impulse to the consolidation of the clinical value of phlebotonics in this indication. METHODS: In light of this, 24 patients with non-complicated chronic venous insufficiency were treated with oral administration of Oligomeric Proanthocyanidins (Pycnogenols-OPC) 100 mg/day. To evaluate the therapeutic efficacy of the treatment, an instrumental evaluation by optical probe capillaroscope was employed in addition to the traditional subjective clinical parameters: swelling, itching, heaviness and pain. The videocapillaroscope examination was performed at the lower third of the leg and the first toe. Edema in the capillaroscopic field, the number of observable capillaries and the capillary dilatation were the parameter chosen to evaluate the efficacy of treatment. All patients completed the study with no reports of adverse events during the period of observation. RESULTS: The results obtained show a positive clinical response (improved or absent symptoms) in over 80% of patients, with significant improvement of symptoms already evident after the first 10 days of treatment. The mechanism of action of the OPCs explains the rapid reduction of the swelling of the lower limbs and correlated with this are the other evaluable symptoms: heaviness and itching. Particularly striking results were observed for itching and pain which completely disappeared during the course of therapy in 80% and 53% of the patients respectively. Noteworthy is the good correlation between the clinical and instrumental data, with improvement in a total of 70% of patients. CONCLUSIONS: The results obtained in the course of this clinical experience, with evident improvement already during the first weeks of treatment, the absence of adverse events added to the benefit of a once-a-day administration, justify the use of OPC in the treatment of non-complicated chronic venous insufficiency.

GREEN TEA EXTRACT

Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis. Below we have selected a few of the many abstracts we have on file showing the benefit of green tea extract.

Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.

ABSTRACT 7:INHIBITORY EFFECT OF SIX GREEN TEA CATECHINS AND CAFFEINE ON THE GROWTH OF FOUR SELECTED HUMAN TUMOR CELL LINES.In: Anticancer Drugs (1996 Jun) 7(4):461-8
Institutional address: Department of Pharmacology and Toxicology College of Pharmacy University of Arizona Tucson 85721 USA.

Green tea is an aqueous infusion of dried unfermented leaves of Camellia sinensis (family Theaceae) from which numerous biological activities have been reported including antimutagenic, antibacterial, hypocholesterolemic, antioxidant, antitumor and cancer preventive activities. From the aqueous-alcoholic extract of green tea leaves, six compounds (+)-gallocatechin (GC), (-)-epicatechin (EC), (-)- epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)- epigallocatechin gallate (EGCG) and caffeine, were isolated and purified. Together with (+)-catechin, these compounds were tested against each of four human tumor cells lines (MCF-7 breast carcinoma, HT-29 colon carcinoma, A-427 lung carcinoma and UACC-375 melanoma). The three most potent green tea components against all four tumor cell lines were EGCG, GC and EGC. EGCG was the most potent of the seven green tea components against three out of the four cell lines (i.e. MCF-7 breast cancer, HT-29 colon cancer and UACC-375 melanoma). On the basis of these extensive in vitro studies, it would be of considerable interest to evaluate all three of these components in comparative preclinical in vivo animal tumor model systems before final decisions are made concerning which of these potential chemopreventive drugs should be taken into broad clinical trials.

GLUTATHIONE AND N-ACETYL-L-CYSTEINE (NAC)

Glutathione and NAC (a major precursor of glutathione) both provide important protection against toxins and free radicals, and can strengthen the immune system. Glutathione is considered to be one of the most important protective substances in the human body with almost 60% of liver detoxification accounted for by this key substance. In addition, glutathione is one of the most potent anti-viral substances known.

Some research has indicated that glutathione may not be able to enter easily into certain types of cells, but NAC is able to enter these cells and be converted into glutathione once inside the cell. Thus, the combination of glutathione and NAC appear to be more potent than either alone.

Reduced glutathione (GSH) is the main intracellular low molecular weight thiol. GSH acts as a nucleophilic scavenger and as an enzyme-catalyzed antioxidant in the event of electrophilic/oxidative tissue injury. Therefore, GSH has a major role as a protector of biological structures and functions. GSH depletion has been recognized as a hazardous condition during paracetamol intoxication. Conversely, GSH rescue, meaning recovery of the protective potential of GSH by early administration of N-acetylcysteine (NAC), has been found to be life-saving. Lack of GSH and electrophilic/oxidative injury have been identified among the causes of the adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and the acquired immunodeficiency syndrome (AIDS). Experimental and early clinical data (in ARDS) point to the role of NAC in the treatment of these conditions. Recently, orally given NAC has been shown to enhance the levels of GSH in the liver, in plasma, and notably in the bronchoalveolar lavage fluid. Rescue of GSH through NAC needs to be appreciated as an independent treatment modality for an array of different disease, all of which have one feature in common: pathogenetically relevant loss of GSH.

N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-Acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.

R-LIPOIC ACID / ALPHA-LIPOIC ACID

R-Lipoic Acid is normally made at low levels in the human body, where it functions primarily as an important metabolic nutrient in the conversion of pyruvic acid into acetyl coenzyme A. As such, it plays a crucial role in the metabolism of both fats and carbohydrates into energy. In addition, r-lipoic acid functions as an extremely powerful antioxidant capable of trapping many different types of free radicals in the body.

Because it is both water and fat soluble, lipoic acid is able to operate in a broader range of body tissues than most other antioxidants. Its small size allows lipoic acid to enter areas of the body not easily accessible to many other substances; this allows lipoic acid, for example, to enter the cell nucleus and prevent free-radical damage to DNA.

Because it is such a powerful antioxidant and can easily function as such in both a reduced and oxidized state, lipoic acid is able to protect other important antioxidants such as glutathione, Vitamin E, and Vitamin C. R-lipoic acid is also able to chelate heavy metals such as lead, cadmium, mercury, free iron, and free copper out of the body.

alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.

Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). However, the underlying molecular mechanism by which α-LA regenerates GSH remains poorly understood. The current study aimed to investigate whether α-LA regenerates GSH by activation of Nrf2 to alleviate cadmium-induced cytotoxicity in HepG2 cells. In the present study, we found that cadmium induced cell death by depletion of GSH through inactivation of Nrf2. Addition of α-LA to cadmium-treated cells reactivated Nrf2 and regenerated GSH through elevating the Nrf2-downstream genes γ-glutamate-cysteine ligase (γ-GCL) and GR, both of which are key enzymes for GSH synthesis. However, blocking Nrf2 with brusatol in the cells co-treated with α-LA and cadmium reduced the mRNA and the protein levels of γ-GCL and GR, thus suppressed GSH regeneration by α-LA. Our results indicated that α-LA activated Nrf2 signaling pathway, which upregulated the transcription of the enzymes for GSH synthesis and therefore GSH contents to alleviate cadmium-induced cytotoxicity in HepG2 cells.

SELENIUM

Selenium has been shown by clinical research to be a key mineral in the body’s defenses against free radicals and has been shown to be a major factor in reducing the symptoms of HIV infections and in the prevention of tumors. Selenium is used in conjunction with glutathione to form the powerful enzyme glutathione peroxidase that is responsible for detoxification of peroxides formed during the process of aerobic metabolism in humans and other animals.

Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis.

The authors performed a controlled trial in 18 top athletes (9 weight lifters and 9 rowers, girls) in order to make evident some chronic and acute effects (antioxidant) of selenium. Nonprotein–SH (essential glutathione), lipid peroxides (MDA-malondialdehyde), glucose-6-phosphate dehydrogenases (G-6-PDH) and fructose-1,6- diphosphate aldolase in serum, have been recorded initially on basal conditions, after 3 weeks of treatment (100 micrograms/day selenium or placebo) and again after 3 weeks of treatment, also on basal conditions, when crossing over the groups (between a free interval of 10 days). In another trial we registered these parameters on basal conditions and after two hours of hard training accompanied by a per oral administration of 150 micrograms selenium (respectively placebo). The results show significant changes under selenium treatment of the peroxides, G-6-PDH and light changes, not significant of the nonprotein–SH, changes which could suggest an antioxidant effect of this element.

VITAMINS B2 and B6 IN COENZYME FORMS

Vitamin B2 as coenzyme riboflavin-5-phosphate is a key vitamin that supports the regeneration of glutathione (via glutathione reductase). Vitamin B6 as coenzyme pyridoxal-5-phosphate is a key vitamin that supports the ability of glutathione to combine with toxic substances (via glutathione transferase) in the process of eliminating them from the body. They are especially effective in their coenzyme forms which allows them to be directly utilized by the body starting in the intestinal tract.

MAGNESIUM, CALCIUM, AND ZINC

Magnesium, zinc, and calcium synergistically work with (and enhance the effects of) the other ingredients in PRO-C. Minerals are especially needed as active components of enzymes that drive metabolic activity. For example, magnesium is required in the functioning of more than 325 types of enzymes.

SUPERIOR, BUFFERED (NON-ACIDIC) FORM OF VITAMIN C. Mineral Ascorbates never acidify your body, keeping you pH balanced. Staying alkaline is an important element in maintaining a healthy body.

RAPID ASSIMILATION. Capsule form ensures rapid uptake and assimilation in the body. You may also empty capsule contents into water, food, or directly Into mouth, if desired. Good, mildly tart taste!

COMPOSITION OF PRO-C™ SUPER ANTIOXIDANT FORMULA

One (1) vegetarian capsule of PRO-C provides the following percentages of the Daily Value:

NUTRIENT

AMOUNT

% Daily Value

Vitamin C (from mineral ascorbates)

500 mg

833%

BioVin® Grape Extract

30 mg

*

Green Tea Extract

30 mg

*

Calcium (from calcium ascorbate)

23 mg

2.3%

Magnesium (from magnesium ascorbate)

23 mg

5.7%

L-Glutathione (reduced)

20 mg

*

N-Acetyl-L-Cysteine (NAC)

15 mg

*

R-Lipoic Acid

5 mg

*

Zinc (from zinc ascorbate)

2 mg

13%

Vitamin B2 (from riboflavin-5′-phosphate)

1 mg

118%

Vitamin B6 (from pyridoxal-5′-phosphate)

1 mg

50%

Selenium (from l-selenomethionine)

10 mcg

*

* No established Daily Value

DIRECTIONS: As a dietary supplement take 1–3 capsules or more daily in divided doses (i.e., spread out over the day), or as recommended by a health care professional. It initially may be useful to take up to 6 capsules per day in divided doses for one week. The contents of the capsule may be emptied into juice or food, as needed.

The Orthomolecular Medicine News Service (OMNS) published on June 12 “The Need for Iodine Supplementation.” We believe strongly in the need for iodine supplementation, especially given the fact that more than 90% of the US population is iodine deficient. For this reason we make available both Nascent Iodine and Lugol’s Iodine Solution 2 to our customers.

We present the full OMNS article (below), as a source of valuable information to our resellers and Creating Health Naturally readers. The factors contributing to massive-scale iodine deficiency remain virtually unchanged over decades. This has led to a greater need for educating health professionals and individuals about the critical importance of iodine supplementation.

The Need for Iodine Supplementation

by Wojciech Rychlik, PhD

(OMNS, June 12, 2017) Feeling tired, having low energy or depression, gaining weight, memory problems, having dry skin, dry mouth, or immune system issues? There is good chance your body needs iodine supplementation. Why iodine? Because this essential to human health element has been singled out as dangerous, for several obscure reasons, and it has been gradually eliminated from our diet, and even worse, replaced by its antagonist, bromine. This trend has been termed, iodophobia (1). It is a cause of widely occurring hypothyroidism in many developed countries.

Iodine: How Much?

Iodine deficiency is associated with (2, 3, 4):

Fibrocystic breast disease leading to breast cancer and stomach cancer

Goiter (enlarged thyroid)

Mental issues from reduced alertness, lowered IQ, autism to cretinism, lack of iodine for the fetus leads to cretinism, and in milder cases to autism and ADHD

High blood pressure, and increased incidence of heart attacks and strokes

The Food and Agriculture Organization (FAO) of the United Nations has published probable safe upper limits for dietary intake of iodine (5). They range from 150 micrograms (mcg) per kilogram (kg) per day in newborn infants to 30mcg/kg/day in adults. That is 2 milligrams (2,000 micrograms) daily for a 146-pound adult. The safe upper limit is higher during pregnancy and lactation (40 mcg/kg/day).

Treatments for Hypothyroidism

The simplest method to deal with an underactive thyroid is proper supplementation with iodine, called orthoiodosupplementation. If the thyroid is damaged, then supplementation with thyroid hormones, thyroxine (T4) and triiodothyronine (T3, the main biologically active hormone) may be necessary. Supplementation (6). with these hormones should be done under close supervision of a medical professional. However, supplementation with inorganic iodine is generally much safer, as the body “knows” how much T4 and T3 need to make. There are also drugs that change physiology of iodine metabolism, but this subject is beyond the scope of this article. Pharmaceutical companies pressure doctors to avoid inexpensive orthoiodosupplementation, so you won’t likely get a prescription for inexpensive Lugol’s solution from a mainstream practitioner.

One caveat to supplementation with iodine is the autoimmune illness called Hashimoto’s disease, or chronic lymphocytic thyroiditis, which is one of the potential causes of hypothyroidism. Unfortunately, when hypothyroidism is diagnosed, the possibility that Hashimoto’s disease underlies this condition has not always been properly tested. Therefore, Hashimoto’s disease has often been misdiagnosed. Doctors usually treat this condition with hormone replacement therapy, and some believe that excessive iodine intake may trigger it in susceptible people (7). Always ask your doctor if iodine supplements are right for you.

History of Iodine Usage and “Iodophobia”

This subject has been covered in detail by Dr. Guy E. Abraham (8,9,10). The iodine element was discovered in 1811 by B. Courtois. In 1850–1853 A. Chatin noted that goiter and cretinism are rare in geological zones rich in iodine and frequent where iodine is in short supply, and that goiter can be prevented by iodine supplementation. In 1895 E. Baumann proposed that iodine is the active element in the thyroid gland.

By the time Bauman identified large concentrations of iodine in the thyroid gland in 1895, pharmaceutical and apothecary preparations containing iodine, excluding thyroid extracts, were widely used as a panacea.

To quote Kelley: (11) “The variety of diseases for which iodine was prescribed in the early years is astonishing – paralysis, chorea, scrofula, lacrimal fistula, deafness, distortions of the spine, hip-joint disease, syphilis, acute inflammation, gout, gangrene, dropsy, carbuncles, whitlow, chilblains, burns, scalds, lupus, croup, catarrh, asthma, ulcers, and bronchitis – to mention only a few. Indeed, tincture of iodine, iodoform, or one of the iodides, was applied to almost every case that resisted the ordinary routine of practice; and between 1820 and 1840 there appeared a remarkable series of essays and monographs testifying to the extraordinary benefits to be achieved by this new and potent remedy.”

Unfortunately, these monographs have virtually disappeared from US medical libraries. In the mid-1800s, iodine treatments of some diseases called for ingestion of gram (1,000 mg) amounts per day. However, most treatments were from 5 to 50 mg daily. The recommended daily amount of iodine by Dr. G. E. Abraham is 0.1-0.3 ml Lugol containing 12.5-37.5 mg elemental iodine. This is the amount of iodine needed for whole body sufficiency, based on a recently reported iodine/iodide-loading test (12). Thyroid gland sufficiency for iodide is achieved with a lower dose.

The first iodophobic authority emerged in early 1900s. Prof. T. Kochler reported that he suffered from overactive thyroid following ingestion of iodide (just a single individual case, not a statistical research study!) Despite this, the number of applications grew. In an International Index published in 1956, and devoted exclusively to iodine pharmaceuticals, no less than 1,700 approved iodine-containing products were listed. In 1948 Wolff and Chaikoff published that a serum inorganic iodide level at a concentration of 1 µM blocks (one micromolar) the synthesis of thyroid hormones, resulting in hypothyroidism and goiter in rats. But this conclusion was erroneous as they even did not measure thyroid hormones in the rats studied, and of course, hypothyroidism and goiter were not observed in those rats. Many organic forms of iodinated drugs were quite poisonous. Unfortunately, medical establishment did not make a distinction between organic and inorganic forms of iodine, and iodophobia became more popular.

Decades ago, iodine was added to bread so that one slice contained 150 mcg of iodine (the current recommended daily allowance). In the 1980s, bromine replaced iodine in bread. Since bromide is an antagonist to iodine (it is goitrogenic), it worsened iodine deficiency in the US. Moreover, a big push to remove salt from our diet (the only grocery item still supplemented with iodine) exacerbated the problem. The only developed nation that resisted iodophobia is Japan, statistically the healthiest and longest living nation on the planet. Their average daily consumption of iodine is around 5 mg, with various reports ranging from 1 mg to 18 mg. In a study of reported daily iodine intake versus total number of clinical symptoms, an intake of approximately 1 mg per day correlated with the lowest number of reported symptoms, that is, the highest level of health (13). Recent popularization of bromides in our food supplies likely increased this amount.

According to Dr. Abraham, (14) “proper amounts of iodine in the food supply should be considered one of a nation’s greatest assets. Removing iodine from the food supply is a major mistake. Supplying a daily intake of iodine sufficient for the whole body (100-400 times the RDA) gives protection against goitrogens and radioactive iodine/iodide fallout; improves immune functions, resulting in an adequate defense system against infection; decreases singlet oxygen formation which is the major cause of oxidative damage to DNA and macromolecules, resulting in an anticarcinogenic effect in every organ; results in a detoxifying effect by increasing urinary excretion of the toxic metals lead, mercury, cadmium, and aluminum, as well as the goitrogens fluoride and bromide; normalizes hormone receptor functions resulting in improved response to thyroid hormones both endogenous and exogenous; and results in better control of blood sugar in diabetic patients; stabilizes cardiac rhythm, obviating the need for the toxic sustained release form of iodine, amiodarone; and normalizes blood pressure without medication in hypertensive patients. Iodine deficiency is the major cause of cognitive impairment, worldwide.”

The Iodine-Cancer Connection

The body requires iodine to metabolize both omega-3 and omega-6 fatty acids. A substance called delta-iodolactone, a derivative of arachidonic acid, which is produced in the thyroid gland and breast tissue, prostate, colon, and the nervous system, is a regulator of a process called cellular apoptosis (“cell death”). Ascorbic acid is required to stimulate intracellular hydrogen peroxide synthesis that, in turn, provides the energy to make iodine free radicals necessary for this reaction. When the level of delta-iodolactone is high enough, the process of apoptosis can then kill cancer cells. (15)

Unfortunately, the recommended daily allowance (RDA) for iodine — about 150 mcg per day — will not allow delta-iodolactone to be efficiently formed in the thyroid gland. The thyroid requires higher iodine concentrations to efficiently produce it. Researchers have found that 100 times the RDA amount of iodine is optimal to produce delta-iodolactone. That equates to taking about 15 mg of iodine per day (15,16). These findings are important because they imply that there are some biochemical reactions that require much larger amounts of iodine than the current RDA. The mechanism by which delta-iodolactone induces cell death may be an important pathway for curing some types of cancer.

Forms of Iodine

Inorganic iodine exists in 6 oxidative states, from -1 to +7. The most reduced form (with most electrons) is iodide (I–); an example is potassium iodide. The diatomic form of elemental iodine I2, has no electrical charge. Monoatomic iodine also has no electrical charge, but is unstable and highly reactive (free radical, labeled as an I with a dot, I* ). It can be produced by exposing I2 to ultraviolet light. Electric and magnetic fields won’t do it, as is sometimes incorrectly suggested. More oxidized forms of iodine are: hypoiodite (I+1), iodite (I+3), iodate (I+5), and periodate (I+7). The body’s metabolism may convert (reduce) these forms to biochemically available iodide, but at the cost of depleting its antioxidants. All forms of positively charged iodine are relatively poisonous, with established lethal doses (LD50) in the range of 35 to 2100 mg/kg. Elemental iodine (I2) and iodides (I–) are non-poisonous. However, a bad “antiseptic” non-culinary taste of iodine (I2) suggests to our senses that this is not so good choice for supplementation.

Despite that adverse taste, almost all the research on iodine supplementation has been done using Lugol’s Solution (17). The original solution is called 5% Lugol’s Iodine, but in reality it consists of 12.5% iodide/iodine or (I–/[I3]–) ions. Two drops of Lugol’s Solution (0.1 ml) contain 12.5 mg iodine/iodide mix. Iodine tablets that are a solid form of Lugol’s solution, were created to mask the taste and make the doses more precise for dietary supplementation.

I should mention a few points about Edgar Cayce’s atomidine. This famous visionary wrote several articles about the best form of iodine supplement (18). Some claim that this was iodine trichloride, but that cannot be true as this compound is toxic by ingestion and damaging to mucous membranes. It decomposes to ICl and poisonous gas Cl2 at 77 degrees C and also in water at room temperature (19). Most likely Cayce’s atomidine was simply a 1% iodine solution (I2) in 95% ethanol. I am surprised that there are educated people, even medical doctors who claim that “elemental monoatomic iodine” preparations (Atomidine, Nascent Iodine etc.) are the best forms of iodine supplements. May be it has something to do with efficient marketing? Elemental Iodine (I2) is soluble in glycerin. Replacement of ethanol with glycerol indeed makes these supplements more consumption-friendly, so they are sold by some vendors as superior products to Cayce’s ethanol-formulated one. Personally, I think glycerol-based I2 supplements are inferior to iodides; however, they are excellent antiseptics.

To defend the validity of Cayce’s vision, in thyroid, I– ion and amino acid tyrosine react through a short intermediate step by forming monoatomic I* free radical (selenium and hydrogen peroxide are involved) to make monoiodotyrosine. Diiodotyrosine is formed analogical way, and finally, two of these molecules combine to produce thyroxine. All those steps are carried by the enzyme thyroid peroxidase, which is normally attached to the protein thyroglobulin. So, yes, monoatomic iodine I* exists in human bodies, and it directly reacts with tyrosine, but no, it wouldn’t be healthy to consume iodine free radicals as their high reactivity would prevent safe transport throughout the body.

In the mid-1930s the thyroid hormone thyroxine became available on the market. This was a blessing for people who had damaged their thyroid. Unfortunately, doctors started to prescribe this hormone to just about anybody with hypothyroidism, thinking that they can control better thyroid hormone levels than our bodies can. And, the “iodine is iodine, no matter what form” mentality became a dangerous trend, because most medical professionals do not fully appreciate the difference between the raw nutrient (iodine) and its product (hormone).

The pharmaceutical industry came up with lots of organic forms of iodine (NB: organic, meaning that iodine is bound to a carbon-atom-containing molecule and NOT meaning it’s grown in a pesticide-free environment), all relatively toxic and certainly not to be used without strict medical supervision. Only inorganic forms of iodine, I– and I2, are safe for supplementation (20,21). Further, high doses of these supplements should still be supervised by your doctor.

Iodine Uses

Iodine plays critical role in human metabolism. Many researchers believe the RDA value of 150 mcg for iodine is too low, especially when this element is commonly substituted with competing element bromine. Therefore, the main use of iodine in dietary supplementation is to enable optimal thyroid function. There are a number of medical conditions where iodine is either essential or helpful. For best results, iodine/iodide should be supplemented with selenium, magnesium, copper (there is usually enough of it in tap water as copper is widely used in plumbing), vitamin B2 (riboflavin) and B3 (niacin). Ask your doctor before taking any iodine supplements, especially if you are on medications.

Elemental iodine (I2) is antibacterial and antifungal, so iodine or iodine/iodide solutions are commonly used topically to sterilize wounds, or internally to fight infections, such as vaginitis and sore throat, and also to sanitize drinking water. Because iodine is antibacterial, drinking it may cause friendly bacterial flora to suffer and result in diarrhea and stomach cramps (the same applies to Lugol’s solution, but to a lesser extent as it contains iodides as well).

Ingestion of iodides prevents the incorporation of destructive radioactive iodine into the body (mainly by the thyroid) in case of nuclear accidents. It also may help flushing already incorporated radioactive iodine from the thyroid, although too much iodine inhibits secretion of T4/T3 from the gland.

Common-Sense Cautions

Overdosing any of the iodine supplements can lead to swollen salivary glands, metallic aftertaste and skin rash and itching (that are usually due to rapid process of detoxification from heavy metals fluorides and bromides), faster heartbeat or palpitations and diarrhea. When supplementation is stopped, these symptoms will usually disappear quickly, often within one day. Iodine stabilizes thyroid hormone production, so it is an adaptogen, but in rare cases, such as acquired allergy to iodine (Hashimoto’s disease), it may actually misbalance it. In some cases, iodine supplementation can cause hypothyroidism, so it’s important to get checked by your doctor to make sure that your thyroid function is not worsened by supplementation. Some authors advising caution are Alan Christianson (22), Jeffrey Dach, (23) and Alan Gaby (24). Testing of levels of thyroid hormones along with testing and supplementation of mineral nutrients such as selenium, zinc, copper, magnesium calcium, and other trace minerals may prevent problems in cases where high doses of iodine/iodide might tend to cause Hashimoto’s disease. (23)

Inorganic Iodine Availability

The most common form of iodine supplement is Lugol’s solution (17). The original solution contains 5% of iodine and 10% iodide. Solid pill forms of Lugol’s solution are sold under several brand names. Potassium iodide (KI), my favorite iodine supplement, is available as tablets as well. Various products with kelp or other seaweed extracts contain iodides as well. Check the label when you buy as some of them are very diluted.

It is difficult to find inexpensive elemental iodine (I2) solution in alcohol. You can buy iodine crystals online and make the proper solution by yourself very easily (using either alcohol or glycerol). The monoatomic iodine concept is simply a marketing gimmick that has been created to inflate the price several fold. Note that if the monoatomic claims were really true, few would really want to drink free radicals, the only monoatomic form that exists. Iodine free radicals are not transported freely in our bodies because they are too reactive. Elemental iodine preparations, including iodine dissolved in glycerol, may be helpful products for external antiseptic use rather than a supplement.

Another form of iodine supplement includes a mixture of algae and thyroid extract in glycerin, water and ethanol. This is likely not harmful because it contains T3 and T4 only in very small amounts, and the recommended serving size is also small. Other complex formulae that contain elemental iodine are a useful antiseptic, but not a good supplement. Iodine trichloride should be avoided as a supplement because it is too toxic.(19)

Summary

The established RDA allowance for iodine (150 mcg/day) is inadequate for many individuals. In order to maintain optimum health, adults need 2-5 mg of iodide daily. Actually, this is in line with the upper safe limit of dietary intake of iodine established by FAO (30 mcg/kg/day). In case of a dysfunctional thyroid or other illnesses, such as fibrocystic breast disease or cancer, 15-50 mg daily may be needed. Ask your doctor about the alternatives to hormone therapy or taking iodine-containing organic drugs, because inexpensive orthoiodosupplementation would usually not be his/her first choice.

The best and safest form of iodine supplementation for a healthy adult is iodide. Iodides are naturally produced in larger quantities by various seaweeds.

Please consult your doctor about iodine supplementation, as in your particular case it may be contraindicated.

A couple years ago, HPDI’s formulator, my father Hank Liers, PhD decided to reformulate our already excellent kids multivitamin—the Kids Mighty-Multi!—to make it better. His intentions were good: the world’s best designer of adult multivitamins would improve the best children’s vitamin.

My quandary? While Dr. Hank was busy at work reformulating our kids multi, the existing—and uber-excellent—original Kids Mighty-Multi! went out-of-stock, and never came back. Suddenly, my seven-year-old son’s “go-to” multivitamin was gone…indefinitely!

I took action—kids vitamins became my obsession—because I wanted the best multivitamin for my child. I searched everywhere for high-quality kids vitamins. Leaving no stone unturned, we tried them all—including organic, whole food, gluten-free, vegan-friendly brands with glossy labels. Did we find good ones? Not really.

What DID we find? Well, not much—and a lot. That is, not much in the way of high potency, high-purity, or advanced forms, like coenzyme vitamins. And a lot of false promises and junk ingredients. Like sugar and corn syrup and GMO ingredients—even from “reputable” brands.

Not to mention artificial sweeteners, colorings, flavorings, as well as toxic preservatives and fillers, which are the de facto standard in conventional products. Natural products are better—not always by as much as you’d expect.

Looking for a good children’s multivitamin? Look no further than chewable Kids Mighty-Multi!

MY MULTIVITAMIN WISHLIST

Now in label-induced miasmic SHOCK…I proposed a reversal of terms. I simply wanted a lot of good things—like complete, balanced nutrients—and not much in the way of toxic additives.

Reeling, I scrawled a brief manifesto or “wishlist” for my ideal kids multivitamin:

Was I asking *too* much? No way. Yet, I was giving up on finding a suitable kids multivitamin. My son instead began taking an HPDI adult multivitamin (Multi Two Caps) we scaled to his sixty five-pound weight. The taste wasn’t great—so we opened capsules directly into his juices and smoothies—because he’s not ready to swallow capsules or tablets whole. At best…a partial solution.

KIDS MIGHTY-MULTI! BACK — BETTER THAN EVER!

Then. It. Happened. Lighting struck—HPDI’s Kids Mighty-Multi! is BACK! Turns out my dad finished reformulating the world’s best kids multivitamin. He broke the news with a smile. Stunned and unbelieving…I took a breath. My heart skipped a beat. Then I grabbed a bottle!

Who knew it would take two years?—and now, who cares!? This month, HPDI proudly introduces a *new* Kids Mighty Multi!. Worth the wait? Yes. Because the new version is better than ever.

A SERIOUS VITAMIN FOR KIDS – FINALLY!

What makes the new Kids Mighty-Multi! so good, and so much better? Let me count the ways. Here is a summary of benefits before I dive into discussing them in greater detail.

• Kids and adults love the taste!

• Full-spectrum of balanced, essential nutrients needed for creating, supporting, and maintaining excellent health for your child. Includes natural coenzyme form vitamins and Krebs’ cycle bionutrients that work with young bodies to provide energy for metabolic processes, healing, and optimal health.

• Functional ingredients built into every aspect of the formula, including the taste-enhancing package, herbal ingredients, and cofactors. Functional ingredients serve multiple purposes in supporting health.

Dr. Hank selected healthy, functional ingredients—as much as possible—in order to enhance the taste. That means these taste enhancers are not only NOT unhealthy like the refined sugars, corn syrups, and artificial sweeteners I found in so many other kids vitamins. But they are GOOD for you!

Because despite what adults might wish, sweeteners still comprise the largest percentage of kids multivitamins by weight. That means your child will be ingesting significant amounts (of whatever these sweeteners are) relative to the size of their multivitamin.

Who wants the bulk of their child’s multivitamin intake comprised of sugars, corn syrup, sucralose, or worse (think aspartame)? This is the reason natural sweeteners providing functional benefits make all the difference for health.

COMPLETENESS MATTERS – A LOT!

Kids Mighty-Multi! is nothing if not complete. As formulated by Dr. Hank Liers, it provides therapeutic levels of all essential vitamins, minerals, cofactors, and much more.

If you read labels (like I do), you’ll see most kids vitamins are “hit-or-miss.” They provide certain nutrients, but often completely miss others—usually with no rhyme or reason. (What was its formulator thinking?)

Missing important nutrients is bad for consumers—like you and your child—because all nutrients require other nutrients to “do a body good.” It’s called synergy, and it’s the way our cells are designed to work.

That means if you obtain sufficient amounts of a specific nutrient, but not enough of another, you may be unable to effectively utilize the nutrient you have—because utilization requires the nutrient you *don’t* have. Catch-22, huh? I’ll talk more about this later.

Kids Mighty-Multi! is nothing if not COMPLETE. (Tablets in photo appear larger than actual size.)

ADVANCED FORMS OF NUTRIENTS…LIKE YOU’VE NEVER SEEN

Then, there are advanced forms of nutrients, like coenzyme B vitamins. Most kids vitamins (and adult multivitamins) offer you the B complex vitamins as synthetic forms. How can you tell? Well, coenzyme vitamin B1 in Kids Mighty-Multi! is from Thiamin Diphosphate and is very different from synthetic “thiamine HCl.” Vitamin B2 is from Riboflavin-5′-Phosphate is not synthetic “riboflavin.” The vitamin B6 is from Pyridoxal-5′-Phosphate is not “pyridoxine HCl.” And so on.

What about vitamin B12 as toxic “cyanocobalamin”? Never. Kids Mighty-Multi! provides coenzyme B12 as methylcobalamin. Other brands sometimes use this form, but then provide synthetic forms for other B vitamins. That makes sense—NOT.

Sure, coenzyme B vitamins cost more to source. But the truth is, your body requires far less coenzyme form vitamins because they are the natural forms found in foods—you easily assimilate and utilize them. Kids Mighty-Multi! doesn’t need large amounts of coenzyme vitamins to give you big benefits.

Meanwhile, synthetic forms are not as easily assimilated—most go through a complex enzymatic breakdown before the body can use them. In some cases (for example if your child lacks certain enzymes due to genetics), syntethic forms cannot be broken down—or used—at all!

Case in point: Folate. Most kids vitamins give you “folic acid,” which is synthetic vitamin B1. A large percentage of the population (including me) lacks the gene providing the enzyme required to process folic acid. If folic acid builds up in cells (because it can’t be broken down), then it can be toxic. Solution: we use coenzyme folate—or 5-MTHF (5-methyl tetrahydrofolate) in Kids Mighty-Multi!. Problem solved.

Recall I said Kids Mighty-Multi! is complete?—and the importance of completeness in a multivitamin? Well, for example, if your kids’ multivitamin only provides synthetic vitamin B6 (as Pyridoxine HCl), it won’t be convertable into its biologically active (coenzyme) form without coenzyme vitamin B1 (Riboflavin-5′-Phosphate).

Did you catch that? To convert Pyridoxine HCl (synthetic vitamin B6) to its usable coenzyme form Pyridoxal-5′-Phosphate, you need coenzyme Riboflavin (Riboflavin-5′-Phosphate). You need a coenzyme form of one B vitamin in order to convert another B vitamin to its coenzyme form!

If you have only synthetic forms of these B vitamins, your body must go through multiple conversion processes in order to first convert synthetic Riboflavin into coenzyme Riboflavin so that you can convert synthetic vitamin B6 (Pyridoxine HCl) into its coenzyme B6 form (Pyridoxal-5′-Phosphate).

Yes, you can *survive* on synthetic forms of B vitamins. But why make your body work so hard? Why survive when you can *thrive* (with coenzyme vitamins)?

Why other kids vitamins don’t include coenzyme forms is BEYOND ME. If other brands go with conventional (and sometimes toxic) synthetic forms, so be it. Run, and go with Kids Mighty-Multi!.

Other advanced forms include vitamin D as D3 (cholecalciferol), vitamin K as K1 and K2 (Menaquinone-7), and minerals using Krebs’ cycle carriers (like citrates, malates, fumarates, succinates, and aspartates) that are best recognized and utilized in the body because they plug into the body’s energy (ATP) production system.

* No established Daily Value
† Quatrefolic® is a registered trademark of Gnosis SPD

SCALABLE DOSING – CALLING ALL KIDS – AND ADULTS!

Maybe the best feature of Kids Mighty-Multi! is scalable dosing. Scalability makes it suitable for children and youth of all sizes—and adults, too!

Glancing at Kids Mighty-Multi!‘s label, you might assume it’s as low potency as the most kids’ vitamins available in stores. Not so fast.

Because Dr. Hank designed this multivitamin for everyone, including adults. How do I know? Because he told me: he takes these chewables himself!

How does it work? You simply take two (2) tablets per 20 pounds of body weight—up to six tablets—for kids. But since most older kids and adults weigh more than 60 pounds, you can take 8–10+ tablets and approximate the nutrition you would get from your regular adult vitamin. How cool is that!

Scalable dosing works well for people who don’t like swallowing capsules or tablets, or who prefer a good-tasting chewable. And who doesn’t, sometimes? It is especially useful for traveling because the entire family can use it.

In my case, I usually take four capsules per day of Hank & Brian’s Mighty Multi-Vite! , which my favorite adult multivitamin, and the inspiration for creating the Kids Mighty-Multi!. Yet, there are many days when I thrill to the taste of the new chewable kids multivitamin—knowing I get a significant amount of nutritional value. That means a lot. A lot of goodness. And not much to worry about.

Dr. Hank Liers pulled out the stops in formulating Kids Mighty-Multi!

CHOOSE KIDS MIGHTY-MULTI!

You’ve got choices. You can go online or to your local natural market, pharmacy, or big box store and fill up on whatever kids vitamins you find. Take your chances. Or you can try Kids Mighty-Multi! to discover how good a children’s multivitamin can (and should) be—a truly superior formula.